Characterization of FimH adhesins expressed by Salmonella enterica serovar Gallinarum biovars Gallinarum and Pullorum: reconstitution of mannose-binding properties by single amino acid substitution

Recombinant FimH adhesins of type 1 fimbriae from Salmonella enterica serovar Gallinarum biovars Gallinarum and Pullorum, in contrast to those of Salmonella enterica serovar Typhimurium, did not bind to high-mannose oligosaccharides or to human colon carcinoma HT-29 cells. However, mutated FimH proteins from biovar Gallinarum and biovar Pullorum, in which the isoleucine at position 78 was replaced by the threonine found in S. enterica serovar Typhimurium, bound well to glycoproteins carrying high-mannose oligosaccharides and colon carcinoma cells. The loss of sugar-binding properties by biovar Gallinarum and biovar Pullorum FimH adhesins, which are a part of the type 1 fimbriae, is most probably the result of a single T78I mutation, as was proven by site-directed mutagenesis of FimH proteins.     

Differential cytokine profile in children with cystic fibrosis

The previously observed occurrence of antineutrophil cytoplasmic autoantibodies (ANCA) in patients who have cystic fibrosis (CF), together with the reported decrease in IgG2, a Th1-controlled isotype, suggests a potential for Th1/Th2 imbalance in CF patients with a possible Th2 predominance. 48 CF patients and 16 controls had levels of IFNgamma, IL-4, and IL-10 measured in supernatants of whole blood cell cultures stimulated by lipopolysaccharide (LPS) and phytohemaglutinine (PHA). The patients were divided into 2 groups: "low responders", having negligible secretion of cytokines (IFNgamma: 10.0-200.0 pg/ml, IL-4: 0.0-0.3 pg/ml) and "high responders", producing high levels of both IFNgamma (500.0-2000.0 pg/ml) and IL-4 (1.0-200.0 pg/ml). There was a statistically significant (P < 0.01) deterioration of lung function measured by an FEV(1) decline by 11.2% over 3 years in the "low responder" group. 10 of 16 "low responders" had chronic lung infections with P. aeruginosa while such infection was less prevalent in the "high responder" group where only 13 of 32 CF patients had positive cultures. A shift towards Th2 response was observed in the "high responder" group as children chronically infected with P. aeruginosa had greater IL-4 production than non-infected CF patients within the same cohort. ANCA autoantibodies were found only in the "high responder" group. Th2 immune response predominance in a subset of CF patients is associated with chronic P. aeruginosa infection.     

Relationship between inflammatory markers and clinical patterns of atrial fibrillation in patients with congestive heart failure

BACKGROUND: Occurence of atrial fibrillation (AF) adversely affects left atrial size and cardiac function. This arrhythmia is also associated with an increase of plasma CRP and fibrinogen concentration. It is not clear whether elevated levels of inflammatory markers in patients with congestive heart failure (CHF) are associated with AF, clinical symptoms or adverse cardiac remodelling. AIM: To investigate the association between levels of inflammatory markers and selected clinical and echocardiographic parameters as well as used treatment in the population of CHF patients with various forms of AF. METHODS: The cross-sectional study included 99 patients with CHF divided into 3 groups. Group I included patients with sinus rhythm. Group II consisted of patients admitted to hospital with AF and discharged with sinus rhythm (the category of paroxysmal and persistent AF). Group III comprised patients with permanent AF. In all patients plasma CRP and fibrinogen concentrations were measured and echocardiographic examination was carried out. Left atrial dimension (LA), ejection fraction (LVEF) and right ventricular systolic pressure (RVSP) were assessed. RESULTS: Mean CRP concentration in group III (5.83+/-5.36 mg/l) was significantly higher than in group I (p=0.001) and group II (p=0.033). In the group with permanent AF mean fibrinogen concentration was elevated to a higher level (391.0+/-77.3 mg/dl) than in group II (p=0.007) and group I (p=0.099). Mean LA and RV dimensions and RVSP in group III were significantly higher than in group I and group II. Multivariable analysis revealed that plasma CRP concentration was significantly associated with the presence of arterial hypertension (p <0.001) and LA enlargement (p=0.007). A significant association between fibrinogen level and CRP level (p=0.038), presence of permanent AF (p=0.045) and metabolic syndrome (p <0.05) was found. Values of ln CRP were significantly correlated with LA diameter (r=0.24; p=0.015). CONCLUSIONS: Increased plasma CRP level in patients with CHF were significantly associated with arterial hypertension and LA enlargement. Permanent form of AF and CRP level have been shown to be significantly associated with increased plasma fibrinogen concentration in the course of CHF.     

Comprehensive treatment for patients with chronic pain in a 12-step based substance use disorder program

Patients with chronic pain (CP) and substance use disorder (SUD) are complex, not yet adequately described, and in need of comprehensive treatments that address both diseases concurrently. Our objectives were to (a) describe a cohort of CP patients who failed traditional treatment (mainly opioids) – then developed opioid use disorder (OUD) and other SUDs and (b) evaluate a comprehensive inpatient treatment program for these patients. Patients were enrolled in an inpatient CP program. Treatment consisted of medical detoxification, group process/education, external and internal qigong, osteopathic manual medicine, and qigong-based mindfulness. Patients also received 20 h per week of 12-step recovery-based SUD treatment. Patients were evaluated at the beginning of treatment (first assessment, day 1–5 range) and at days 30 and 45. Assessments were: Beck Depression Inventory-II, Brief Pain Inventory, West Haven-Yale Multidimensional Pain Inventory (patient section), and McGill Pain Questionnaire. The Global Impression of Change Scale was administered at day 45. A mixed model analysis was used to evaluate treatment progress. Demographic data revealed an older cohort with OUD, other SUDs, and multiple pain diagnoses who failed traditional treatment. Questionnaire evaluations were consistent and similar across all of the above measures: patients’ scores showed marked, statistically significant improvements in depression, pain, and quality of life ratings. The most substantial improvements occurred between the first and second assessments. The findings are sufficiently encouraging to warrant further evaluation of the protocol and to plan comparative studies.     

The role of neurotrophic factors in the pathology and treatment of multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating disease of primary autoimmune origin with essential component of subsequent axonal degeneration. It has been found that inflammatory cells crucial for MS pathogenesis are able to release neurotrophic factors (NFs). Thus the concept of neuroprotective effect of inflammation has arisen. Over recent years, increasing number of studies has revealed that NFs play an important role in MS and its animal model — experimental autoimmune encephalomyelitis (EAE). In the current review the evidence for the role of NFs in MS pathogenesis the same as their remarkable potential in MS therapy is presented.     

Amiodarone induced pneumonitis and hyperthyroidism: case report

Amiodarone is a highly effective antiarrhythmic agent used in life-threatening ventricular and supraventricular arrhythmias. Its long-term use may however lead to several adverse effects, including corneal deposits, liver and thyroid gland dysfunction, lung lesions, bone marrow injury, skin lesions, or neurological abnormalities. The article presents the case of a 56-year-old man with a history of a stroke, who after a few days of amiodarone therapy for an episode of atrial fibrillation was diagnosed with amiodarone-induced hyperthyroidism and interstitial pulmonary lesions. Clinical and laboratory symptoms of hyperthyroidism and radiographic signs of pulmonary involvement did not occur until several weeks after discontinuation of amiodarone therapy. Differential diagnosis of causes of hyperthyroidism and diseases causing nodular pulmonary lesions did not demonstrate any other pathologies. Empirical antibiotic therapy and administration of thiamazole and high doses of propranolol failed to improve the patient's clinical status. It was not until thiamazole was given in combination with glucocorticosteroids, when a slow relief of hyperthyroidism symptoms and resolution of radiographic pulmonary signs were observed. Based on the presented case, the risk of appearance of 2 serious concomitant adverse effects was demonstrated, even following a short-term amiodarone therapy. This paper also contains an overview of adverse effects which may be encountered during or after therapy with this effective antiarrhythmic agent. It was emphasized how important it is to select patients appropriately, and to monitor potential adverse effects during amiodarone therapy.     

Cross-cultural adaptation and validation of the health literacy assessment tool METER in the Portuguese adult population

Objective

We aimed to culturally adapt and validate METER in the Portuguese population, and to define cut-off values for adequate health literacy.

Methods

We used the standard procedure for the adaptation of the words and surveyed health professionals to select the non-words. The instrument was administered to a total sample of 249 participants and retested in a sub-sample of 45 after three months. Cut-offs were defined using the modified Angoff procedure. Construct validity was assessed through association with educational attainment and health-related occupation.

Results

Exploratory factor analysis revealed two dimensions of the instrument, one for words and another for non-words. METER showed a high degree of internal consistency, and acceptable test–retest reliability. Adequate health literacy was defined as scoring at least 35/40 in words and 18/30 in non-words. Physicians scored higher than any other group, followed by health researchers, researchers from other areas and by people with progressively lower levels of education (p < 0.001).

Conclusion

We culturally adapted a brief and simple instrument for health literacy assessment, and showed it was valid and reliable.

Practice implications

The Portuguese version of METER can be used to assess health literacy in Portuguese adults and to explore associations with health outcomes.     

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease

Introduction

CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy.

Material and methods

The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique.

Results

IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A’ in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher R_V5(6) and R_V5(6) + S_V1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes.

Conclusions

Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.     

Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,^1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.^4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).⁷The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.^8,9 The significant physiologic variation of the normal Hb range with age¹⁰ and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.¹¹The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes.